Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate, and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected with H5N1 Bird Flu Virus Full article
Journal |
Molecular Biology
ISSN: 0026-8933 , E-ISSN: 1608-3245 |
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Output data | Year: 2017, Volume: 51, Number: 4, Pages: 633-638 Pages count : 6 DOI: 10.1134/S0026893317040136 | ||||||||
Tags | conjugates, influenza A virus, inhibitors, nanoparticles, oligonucleotides, replication | ||||||||
Authors |
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Affiliations |
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Funding (3)
1 | Russian Foundation for Basic Research | 15-04-04109 |
2 | Russian Science Foundation | 16-15-10073 |
3 | Russian Science Foundation | 15-15-00121 |
Abstract:
We have previously described nanocomposites containing conjugates or complexes of native oligodeoxyribonucleotides with poly-L-lysine and TiO2 nanoparticles. We have shown that these nanocomposites efficiently suppressed influenza A virus reproduction in MDCK cells. Here, we have synthesized previously undescribed nanocomposites that consist of TiO2 nanoparticles and polylysine conjugates with oligonucleotides that contain phosphoryl guanidine or phosphorothioate internucleotide groups. These nanocomposites have been shown to exhibit antiviral activity in MDCK cells infected with H5N1 influenza A virus. The nanocomposites containing phosphorothioate oligonucleotides inhibited virus replication ~130-fold. More potent inhibition, i.e., ~5000-fold or ~4600-fold, has been demonstrated by nanocomposites that contain phosphoryl guanidine or phosphodiester oligonucleotides, respectively. Free oligonucleotides have been nearly inactive. The antiviral activity of oligonucleotides of all three types, when delivered by Lipofectamine, has been significantly lower compared to the oligonucleotides delivered in the nanocomposites. In the former case, the phosphoryl guanidine oligonucleotide has appeared to be the most efficient; it has inhibited the virus replication by a factor of 400. The results make it possible to consider phosphoryl guanidine oligonucleotides, along with other oligonucleotide derivatives, as potential antiviral agents against H5N1 avian flu virus.
Cite:
Levina A.S.
, Repkova M.N.
, Chelobanov B.P.
, Bessudnova E.V.
, Mazurkova N.A.
, Stetsenko D.A.
, Zarytova V.F.
Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate, and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected with H5N1 Bird Flu Virus
Molecular Biology. 2017. V.51. N4. P.633-638. DOI: 10.1134/S0026893317040136 WOS Scopus РИНЦ
Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate, and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected with H5N1 Bird Flu Virus
Molecular Biology. 2017. V.51. N4. P.633-638. DOI: 10.1134/S0026893317040136 WOS Scopus РИНЦ
Original:
Левина А.С.
, Репкова М.Н.
, Челобанов Б.П.
, Бессуднова Е.В.
, Мазуркова Н.А.
, Стеценко Д.А.
, Зарытова В.Ф.
Влияние способа доставки на противовирусную активность фосфодиэфирных, тиофосфатных и фосфорилгуанидиновых олигонуклеотидов в клетках MDCK инфицированных вирусом птичьего гриппа A (H5N1)
Молекулярная биология. 2017. Т.51. №4. С.717-723. DOI: 10.7868/S0026898417040139 RSCI Scopus РИНЦ
Влияние способа доставки на противовирусную активность фосфодиэфирных, тиофосфатных и фосфорилгуанидиновых олигонуклеотидов в клетках MDCK инфицированных вирусом птичьего гриппа A (H5N1)
Молекулярная биология. 2017. Т.51. №4. С.717-723. DOI: 10.7868/S0026898417040139 RSCI Scopus РИНЦ
Dates:
Submitted: | Jul 5, 2016 |
Accepted: | Oct 15, 2016 |
Published print: | Jul 1, 2017 |
Published online: | Aug 23, 2017 |
Identifiers:
Web of science | WOS:000408217400020 |
Scopus | 2-s2.0-85028350458 |
Elibrary | 31055078 |
Chemical Abstracts | 2017:1372907 |
OpenAlex | W4249494374 |